Iron Metabolism Disorders for Cognitive Dysfunction After Mild Traumatic Brain Injury.

Suna Huang,Su Li,Yujie Chen,Hua Feng

doi:10.3389/fnins.2021.587197

Suna Huang, Su Li + Show 2 more

Open Access

https://doi.org/10.3389/fnins.2021.587197

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Abstract

Traumatic brain injury (TBI) is one of the most harmful forms of acute brain injury and predicted to be one of the three major neurological diseases that cause neurological disabilities by 2030. A series of secondary injury cascades often cause cognitive dysfunction of TBI patients leading to poor prognosis. However, there are still no effective intervention measures, which drive us to explore new therapeutic targets. In this process, the most part of mild traumatic brain injury (mTBI) is ignored because its initial symptoms seemed not serious. Unfortunately, the ignored mTBI accounts for 80% of the total TBI, and a large part of the patients have long-term cognitive dysfunction. Iron deposition has been observed in mTBI patients and accompanies the whole pathological process. Iron accumulation may affect long-term cognitive dysfunction from three pathways: local injury, iron deposition induces tau phosphorylation, the formation of neurofibrillary tangles; neural cells death; and neural network damage, iron deposition leads to axonal injury by utilizing the iron sensibility of oligodendrocytes. Thus, iron overload and metabolism dysfunction was thought to play a pivotal role in mTBI pathophysiology. Cerebrospinal fluid-contacting neurons (CSF-cNs) located in the ependyma have bidirectional communication function between cerebral–spinal fluid and brain parenchyma, and may participate in the pathway of iron-induced cognitive dysfunction through projected nerve fibers and transmitted factor, such as 5-hydroxytryptamine, etc. The present review provides an overview of the metabolism and function of iron in mTBI, and to seek a potential new treatment target for mTBI with a novel perspective through combined iron and CSF-cNs.

Highlights

Traumatic brain injury (TBI) is a general term for pathological or structural changes in the brain caused by impact, bumps, penetrating injuries, or blasting under external forces (Menon et al, 2010; Cook and Hawley, 2014; Pavlovic et al, 2019), which involves at least one of the following symptoms: loss or a decreased level of consciousness, loss of memory for events before or after the injury, neurological deficits, or alterationsIron Metabolism Disorders After TBI in mental state
Studies have shown that the expression of ferritin, transferrin, and transferrin receptors in the brain is increased after intracranial hemorrhage (Wu et al, 2003), which may increase iron absorption in neurons and oligodendrocytes, which is consistent with previous reports that iron accumulates in brain cells after TBI
Our research team has confirmed that iron deposition around the ventricle and ependymal cilia damage occur after intraventricular hemorrhage (IVH), potentially representing a new TBI treatment target, and may be related to the long-term recovery of cognitive function

Summary

Introduction

Traumatic brain injury (TBI) is a general term for pathological or structural changes in the brain caused by impact, bumps, penetrating injuries, or blasting under external forces (Menon et al, 2010; Cook and Hawley, 2014; Pavlovic et al, 2019), which involves at least one of the following symptoms: loss or a decreased level of consciousness, loss of memory for events before or after the injury, neurological deficits (weakness, loss of balance, changes in vision, etc.), or alterationsIron Metabolism Disorders After TBI in mental state (confusion, disorientation, slowed thinking, etc.). The increased iron in the interstitium and CSF will be transported to various types of nerve cells in various forms, eventually leading to iron accumulation in nerve cells, which can produce large amounts of ROS to intensify oxidative stress and aggravate secondary damage after TBI (Nunez et al, 2012).

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Conclusion